Lecture #31 from the Drug Delivery Foundation's 2010 Oral Drug Delivery Conference: http://www.ddfint.org/previous-events/2017/4/22/odd2010-strategies-for-oral-drug-delivery

1. Gordon L Amidon
College of Pharmacy
University of Michigan
Ann Arbor, MI 48109

2.  GI Physiology: Transport Mechanistic
 Permeability &Transit
 Physical Chemistry: InVivo Dissolution
 Solubility/Dissolution
 Biopharmaceutical Evaluation: Mechanistic
 InVivo-InVitro
 Dosage FormTechnology: Optimization of Delivery
 IR and MR
 Regulatory Advances: Separate BE and BA Science
 Essential Standard to Insure Label Claims

3. Efficacy
Safety
Half life
Bioavailability
Dose is actually a surrogate of BA

4. 1970’s
Descriptive
/ Empirical
1980’s
Mechanistic/
Organ
1990’s
Tissue/
Cell
2000’s
Genomic/
Membrane
1960
Biopharmaceutics:
The Beginning

5. ∫∫∫ ⋅∞=
t
A
effabs CdAdtPMtMF
0
)(/)(

8. Unknown localization: HPT1, CAT-1, EAAC1, CNT, CNT2, ENT1, ENT2, SAAT1, NBC2,
NPT4, NAPI-3B, SVCT1-2, FAT
Fig. A. Localization of intestinal membrane transporters and their coupling for nutrients and drug absorption. Arrows indicate
the direction of transport. Dashed arrows indicate the coupling of apical transporters with basolateral transporters. rBAT and
b0,+AT form a complex for functional transporter. HLAT and 4F2hc, hy+ LAT and 4F2hc also form a transporter complex.
Apical membraneIntestinal lumen Basal membrane
rBAT
4F2hc
ATB0
TAUT
b0,+AT
hPepT1
MCT1
MOAT
MDR
IBAT
FATP4
SGLT1
GLUT5 GLUT2
OCT1
OCT3
ILBP
HLAT ?
hy+ LAT ?
?
?
?
?

12. Label
Product
Efficacy
&
“BE”

15. August 2000 FDA Guidance
Amidon et al.., Pharmaceutical Research, 12, 413
(1995).

16. Biopharmaceutics
History: What
Happened
1960 : Limited Technology
1990: A BA View
2010: Molecular Mechanism

18.  Mechanistic
 GI Physiology and Product Dissolution
 Focused on Product: BE and labeling
 Dissolution Methodology and BCS InVivo
Relevance
 Mechanistic ADME: BCS and BDDCS